普伐他汀调脂对肾小球硬化防治作用的实验研究  

LIPID LOWERING EFFECT OF PRAVASTATIN ON GLOMERULOSCLEROSIS PROTECTION AND TREATMENT

作　　者：鲁盈[1,2] 李惊子[1,2] 郑欣[1,2] 赵春玉[1,2] 洪健美[1,2] 邹万忠 王海燕[1,2] 

机构地区：[1]北京医科大学第一医院肾内科 [2]北京医科大学肾脏病研究所

出　　处：《中华内科杂志》1997年第4期242-245,共4页Chinese Journal of Internal Medicine

基　　金：国家自然科学基金

摘　　要：为了解普伐他汀调脂对肾小球硬化的影响，采用嘌呤霉素肾病综合征动物模型，其肾脏病理类似人类局灶节段肾小球硬化。实验分正常、肾病对照和肾病治疗三组，普伐他汀灌胃给药６ｍｇｋｇ－１ｄ－１，实验共１２周。观察血清脂谱和肾脏病理。结果显示：肾病治疗组血清总胆固醇、甘油三酯、极低密度脂蛋白和高密度脂蛋白均明显低于肾病对照组（Ｐ＜０．０５）；同时肾组织损伤也明显减轻，两组肾小球硬化指数差异有显著性（Ｐ＜０．０１）；免疫组化和计算机图像半定量分析进一步显示肾病治疗组细胞外基质成分（Ⅲ、Ⅳ型胶原，纤维连接蛋白，层粘连蛋白）肾小球内聚积程度明显少于肾病对照组。肾病治疗组血清肌酐和尿素氮亦低于肾病对照组。而两组间血清白蛋白和尿蛋白差异无显著性。提示高脂蛋白血症在肾脏疾病进展的病理生理中起重要作用，而调脂药物能减缓肾小球硬化和保护肾功能。The lipid lowering effect of pravastatin on glomerulosclerosis was observed in nephrotic syndrome model, which was induced in rats by using repeated puromycin injections. The histologic changes of the model were similar to those of human focal segmental glomerulosclerosis. Rats were divided into three groups, namely, normal control, nephropathy and nephropathy with pravastatin. Pravastatin was administered through gastric tube 6mg·kg -1 ·d -1 for 12 weeks. The lipoprotein profile and histologic development were observed. The results showed that pravastatin treated rats had significantly lower cholesterol, triglycerides, very low density lipoprotein and high density lipoprotein than the nephropathy group at 7 weeks ( P <0.05). Moreover, the renal damage was also less marked in pravastatin treated rats. Light microscopic and immunohistochemical examination revealed that lipid lowering therapy was associated with significant lower level of glomerular sclerosing index and less accumulation of extracellular matrix including collagen Ⅲ、Ⅳ, laminine and fibronectin as compared with the nephropathy group. However urinary protein and serum albumin levels were similar in both groups. It is suggested that lipid lowering thyrapy may retard the progression of glomerulosclerosis and thus preserve renal function. The results imply that hyper lipoidemia plays an important role in the pathophysiological progression of renal disease.

关 键 词：肾小球硬化症 普伐他汀 药物疗法 降脂药 

分 类 号：R692.605[医药卫生—泌尿科学] R972.6[医药卫生—外科学]